Thesis (Ph. D.)--University of Wisconsin--Madison, 1950. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [156]-167).

Thesis (M.S.)--University of Wisconsin--Madison, 1947. / Typescript. Contains reprints from Journal of Bacteriology. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1965. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1961. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 62-64).

Thesis (M.S.)--University of Wisconsin--Madison, 1962. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 52-56).

Thesis (M.S.)--University of Wisconsin--Madison, 1962. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 48-52).

Thesis (M.S.)--University of Wisconsin--Madison, 1962. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 37-38).

Brucellosis is an important zoonotic disease of nearly worldwide distribution. Despite the availability of live vaccine strains for bovine (S19, RB51) and small ruminants (Rev 1), these vaccines have several drawbacks including residual virulence for animals and humans. Safe and efficacious immunization systems are therefore needed to overcome these disadvantages. Brucella melitensis and Brucella abortus mutants in the luxR gene were generated and investigated for theri potential use as improve vaccine candidates. Immunization with a sustained release vehicle to enhance vaccination efficacy was evaluated utilizing the live mutants in encapsulated alginate microspheres containing a non-immunogenic eggshell precursor protein of the parasite Fasciola hepatica (Vitelline protein B, VpB). BALB/c mice were immunized with either encapsulated or nonencapsulated vaccine candidates to evaluate immunogenicity, safety and protective efficacy. The results suggest that luxR mutants, are attenuated in the mouse and macrophage model and appear good and safe vaccine candidates when the immunogen is given in a microencapsulated format. We were also able to demonstrate the utility of microencapsulation in oral delivery by increasing vaccine performance of current licensed vaccine strains in a natural host, the Red Deer. Together, these results suggest that microencapsulation of live Brucella produces an enhanced delivery vaccine system against brucellosis increasing the efficacy of poorly-performing nonencapsulated vaccine candidates.

Historical data suggests that prolonged survival of Brucella vaccine organisms in the target host enhances immune protection. Recent research has focused upon the development of rough vaccine strains to avoid interference with standard diagnostic tests. Rough organisms are rapidly cleared from the host, however. In an effort to develop improved vaccine strains, we have screened signature tagged mutagenesis banks to identify mutants with varying survival characteristics. We hypothesize that in order for a vaccine to be efficacious, it must survive in the host. In order to test this, we constructed marked and unmarked deletion mutants of B. abortus and B. melitensis in genes previously demonstrated by transposon mutagenesis to attenuate in vivo and in vitro virulence. Survival and efficacy of these novel deletion mutants were then evaluated in the mouse model. The asp24 mutants, which persist for extended periods in vivo, appear superior as a vaccine candidate compared to approved vaccine strains S19 and Rev1 in the mouse model against either homologous or heterologous challenges. Once enhanced protection against infection was demonstrated in the mouse, components of immune function that appeared to be most important were identified to correlate the immune response with the observed protection. We demonstrated that the most persistent mutant, delta-asp24, affords the greatest protection in mice against virulent challenge. In order to evaluate safety of the novel vaccine strains as well as protection against infection and abortion, we tested selected B. melitensis unmarked deletion mutants in a natural host, the goat. The delta-asp24 mutant was shown to be safe in pregnant goats while providing significant protection against infection and abortion.

Thesis (D.P.H.)--University of Michigan.